Downregulation of miR-27a* and miR-532-5p and Upregulation of miR-146a and miR-155 in LPS-induced RAW264.7 Macrophage Cells

Cheng, Ying; Kuang, Wenhua; Hao, Yuanyuan; Zhang, Donglin; Lei, Ming; Du, Lijun; Hu, Jiao; Zhang, Xiaoru; Wang, Fengyang

doi:10.1007/s10753-012-9443-8

Cited by 65 publications

(65 citation statements)

References 22 publications

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“…miRNAs are involved in the regulation of diverse processes, including apoptosis, metabolism, cell fate determination, and host-pathogen interactions (9). miRNAs have been shown to regulate the host antiviral response by altering the expression of host genes required for virus replication and antiviral response (10)(11)(12) or by directly targeting viral genomes and/or transcripts (13)(14)(15)(16)(17).…”

mentioning

confidence: 99%

Human MicroRNA miR-532-5p Exhibits Antiviral Activity against West Nile Virus via Suppression of Host Genes SESTD1 and TAB3 Required for Virus Replication

Slonchak

Shannon

Pali

et al. 2016

J Virol

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West Nile virus (WNV) is a mosquito-transmitted flavivirus that naturally circulates between mosquitos and birds but can also infect humans, causing severe neurological disease. The early host response to WNV infection in vertebrates primarily relies on the type I interferon pathway; however, recent studies suggest that microRNAs (miRNAs) may also play a notable role. In this study, we assessed the role of host miRNAs in response to WNV infection in human cells. We employed small RNA sequencing (RNA-seq) analysis to determine changes in the expression of host miRNAs in HEK293 cells infected with an Australian strain of WNV, Kunjin (WNV KUN ), and identified a number of host miRNAs differentially expressed in response to infection. Three of these miRNAs were confirmed to be significantly upregulated in infected cells by quantitative reverse transcription (qRT)-PCR and Northern blot analyses, and one of them, miR-532-5p, exhibited a significant antiviral effect against WNV KUN infection. We have demonstrated that miR-532-5p targets and downregulates expression of the host genes SESTD1 and TAB3 in human cells. Small interfering RNA (siRNA) depletion studies showed that both SESTD1 and TAB3 were required for efficient WNV KUN replication. We also demonstrated upregulation of mir-532-5p expression and a corresponding decrease in the expression of its targets, SESTD1 and TAB3, in the brains of WNV KUN -infected mice. Our results show that upregulation of miR-532-5p and subsequent suppression of the SESTD1 and TAB3 genes represent a host antiviral response aimed at limiting WNV KUN infection and highlight the important role of miRNAs in controlling RNA virus infections in mammalian hosts. IMPORTANCEWest Nile virus (WNV) is a significant viral pathogen that poses a considerable threat to human health across the globe. There is no specific treatment or licensed vaccine available for WNV, and deeper insight into how the virus interacts with the host is required to facilitate their development. In this study, we addressed the role of host microRNAs (miRNAs) in antiviral response to WNV in human cells. We identified miR-532-5p as a novel antiviral miRNA and showed that it is upregulated in response to WNV infection and suppresses the expression of the host genes TAB3 and SESTD1 required for WNV replication. Our results show that upregulation of miR-532-5p and subsequent suppression of the SESTD1 and TAB3 genes represent an antiviral response aimed at limiting WNV infection and highlight the important role of miRNAs in controlling virus infections in mammalian hosts. W est Nile virus (WNV) is a mosquito-transmitted flavivirus associated with outbreaks of encephalitis in humans and horses around the world (1). The most significant WNV outbreaks have occurred in North America, where a highly pathogenic strain of WNV emerged in New York in 1999. This strain rapidly spread to all the states and by 2011 had infected an estimated 1.8 million people, causing close to 360,000 illnesses and ϳ1,300 deaths (2). The majority of ...

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confidence: 99%

Human MicroRNA miR-532-5p Exhibits Antiviral Activity against West Nile Virus via Suppression of Host Genes SESTD1 and TAB3 Required for Virus Replication

Slonchak

Shannon

Pali

et al. 2016

J Virol

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“…**p50.01 and ***50.001 when compared with corresponding control samples. Cheng et al, 2012;Ruggiero et al, 2009;Tili et al, 2007;Zheng et al, 2012) and miR-125b (Androulidaki et al, 2009;El Gazzar & McCall, 2010;Murphy et al, 2010;Tili et al, 2007) have been shown to be involved in the LPS-induced regulation of TNF-a expression. In macrophages, the expression levels of miR-155 are known to be induced by LPS treatment, while those of miR-125b are reduced (Tili et al, 2007).…”

Section: Suppression Of Fascin Expression Results In Alterations Of Mmentioning

confidence: 99%

Fascin Regulates TLR4/PKC-mediated Translational Activation Through miR-155 and miR-125b, which Targets the 3′ Untranslated Region of TNF-α mRNA

Kim

Jang

Suk

et al. 2015

Immunological Investigations

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Fascin is a well-known cytoskeletal regulatory protein that, as a substrate of protein kinase C (PKC), is involved in PKC-mediated translational regulation of TNF-α in macrophages stimulated with lipopolysaccharide (LPS). The regulatory effects of fascin targeted the 3'-untraslated region (UTR) of the TNF-α mRNA, and suppression of PKC activity or fascin expression resulted in specific blockage of the LPS-induced translational activation of the mRNA. In an effort to identify the molecular mechanism of this fascin-mediated translational regulation, the expression levels of micro-RNA (miRNA) after stimulation of the toll-like receptor 4 (TLR4) signaling pathways were analyzed in cells with down-regulation of fascin. The LPS-induced translation of TNF-α is known to be regulated by miR-155 and miR-125b, which have positive and negative effects, respectively. Interestingly, suppression of fascin expression reversed LPS-induced down-regulation of miR-125b and abolished the LPS-induced increase in miR-155. Furthermore, introduction of miR-155 precursor, blocking of miR-125b activity, or introduction of a mutation into the miR-125b binding site of the TNF-α 3'-UTR restored translational activation in cells with suppressed fascin expression. These data indicate that fascin regulates translation through miR-155 and miR-125b, which target 3' UTR in TNF-α mRNA.

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“…Gram-negative bacterial cell walls contain LPS endotoxins, which are well known to increase miR-146a and miR-155 in RAW264.7 macrophages and miR-146a, miR-132, and miR-155 in THP-1 monocytes in vitro [23, 37]. A previous study of human periodontal disease gingiva found miR-146a increased but miR-155 reduced relative to healthy tissues [38].…”

Section: Discussionmentioning

confidence: 99%

Polymicrobial infection alter inflammatory microRNA in rat salivary glands during periodontal disease

et al. 2016

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Periodontal disease initiated by subgingival pathogens is linked with diminished secretion of saliva, and implies pathogenic bacteria dissemination to or affects secondary sites such as the salivary glands. MicroRNAs activated in response to bacteria may modulate immune responses against pathogens. Therefore, Sprague-Dawley rats were infected by oral lavage consisting of polymicrobial inocula, namely Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, or sham-infected for 12 weeks (n=6). We quantified inflammatory miRNA expression levels of miRNA-132, miR-146a, and miR-155 at secondary sites to the primary infection of the gingiva, including submandibular salivary glands, lacrimal glands, and pancreas. The presence of bacteria was detected in situ at secondary sites. Infected rat gingiva showed increased relative expression of miR-155. In contrast, miRNA-155 expression was decreased in submandibular salivary glands, along with positive identification of P. gingivalis in 2/6 and T. denticola in 1/6 rat salivary glands. Furthermore, miRNA-132 and miRNA-146a were significantly decreased in the pancreas of infected rats. This study is the first to show primary periodontal infections can alter miRNA profiles in secondary sites such as the salivary gland and pancreas. Whether these alterations contribute to pathologies of salivary glands in Sjögren’s syndrome or of pancreas in diabetes warrants further investigation.

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Downregulation of miR-27a* and miR-532-5p and Upregulation of miR-146a and miR-155 in LPS-induced RAW264.7 Macrophage Cells

Cited by 65 publications

References 22 publications

Human MicroRNA miR-532-5p Exhibits Antiviral Activity against West Nile Virus via Suppression of Host Genes SESTD1 and TAB3 Required for Virus Replication

Human MicroRNA miR-532-5p Exhibits Antiviral Activity against West Nile Virus via Suppression of Host Genes SESTD1 and TAB3 Required for Virus Replication

Fascin Regulates TLR4/PKC-mediated Translational Activation Through miR-155 and miR-125b, which Targets the 3′ Untranslated Region of TNF-α mRNA

Polymicrobial infection alter inflammatory microRNA in rat salivary glands during periodontal disease

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